The objective of this research project is to elucidate the mechanisms of action of the alpha-adrenergic catecholamines in influencing cellular events. To this end, the identification of alpha-adrenergic receptors, their biochemical links in the plasma membrane of the cell, and physiological concomitants of alpha-adrenergic actions will be investigated in detail. The proposal has become feasible by the recent availability of a very useful radioiodinated ligand with which alpha-adrenergic receptors may be studied directly, and by the development of appropriate cellular models. The specific goals of the project are to characterize alpha-adrenergic receptors and to study their regulation in myocardial membranes, cultured primary myocardial cells, and certain cultured cell lines; to test the hypothesis that the biochemical mediators of alpha-adrenergic receptor activation are linked directly to effects upon the cyclic AMP complex of the cell, to phospholipid metabolism, or to the calcium ion; to relate pharmacological responses of; the cell to occupation of alpha-adrenergic receptors; and to conduct a careful structure-function-binding analysis of the alpha-adrenergic catecholamines. It is anticipated that this research plan will foster the candidate's development into an independent investigator and will build effectively upon the research base that she has already established. Several factors will be important in achieving both the scientific and personal goals of the proposal. They include the resources of the College of PHysicians and Surgeons, the Department of Medicine, and the Sponsor as well as the scientific expertise that will be available to the candidate throughout the duration of the research project.